Cupric Halide‐Mediated Intramolecular Halocyclization of N‐Electron‐Withdrawing Group‐Substituted 2‐Alkynylanilines for the Synthesis of 3‐Haloindoles

Abstract

A convenient and efficient method for the synthesis of 3-haloindoles has been developed. Both 3-chloro-and 3-bromoindole derivatives can be obtained in high yields by the reaction of N-electron-withdrawing group-substituted 2-alkynylanilines with cupric halide in dimethyl sulfoxide (DMSO) within a short period of time. Investigation of the reaction mechanism reveals that two equivalents of cupric halide are necessary.

Copper-Catalyzed Synthesis of Trifluoroethylarenes from Benzylic Bromodifluoroacetates

“…General Procedure A was followed using [1-(methylsulfonyl)-1 H -indol-2-yl]methanol 18 (1.1 g, 5.0 mmol). Workup and chromatographic purification (hexanes/EtOAc 1:0→9:1) provided the title compound as a grey solid (1.1 g, 70%).…”

Efficient synthesis of indoles from 2-alkynylaniline derivatives in water using a recyclable copper catalyst system

“…22 However, many problems, especially those related to the tolerance of the functional group towards alkaline conditions, remained unresolved until the pilot work employing Cu(II) catalysts reported by Hiroya et al 22 in 2004, in which either sulfonamides or unsubstituted primary and secondary aniline derivatives could be cyclized into corresponding indoles. Henceforth, copper 18,22,[40][41][42][43][44][46][47][48]53,54 and many other inexpensive catalysts (metal or nonmetal, such as Hg [55][56][57] , Zn 58-61 and I 62 ) have received much attention for use in functionalized indole synthesis, although noble metals are necessary for some special purposes. 14,28,30,34,63 Water is the most environmentally benign and inexpensive medium, and its use often leads to the observation of unique reactivity and a simplified separation process.…”

“…As a result, a large number of methods, especially, various cyclizations, have been well developed after the first practical indole synthesis was reported by Fischer and Jourdan in 1883. 1,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] In particular, the introduction of transition metal reagents as catalysts (such as palladium, [19][20][21][22][23][24] gold, 5,10,14,25-28 rhodium, [29][30][31][32] ruthenium, 27,31,[33][34][35][36] platinum, 37 copper 6,18,22,[38][39][40][41][42][43][44][45][46][47][48] ) has deeply improved on the synthesis of indole and its derivatives. Among them, the ring closing of 2-ethynylaniline derivatives or their precursors (such as 2-bromo-anilines), 5,[49][50][51...…”

Green synthesis of halogenated thiophenes, selenophenes and benzo[b]selenophenes using sodium halides as a source of electrophilic halogens

“…27 When Cu 2 SO 4 •5H 2 O is mixed with NaCl in ethanol, the resulting CuCl 2 can weakly coordinate with alkyne 5 , followed by an anti-attack from a nearby S nucleophile to give the intermediate 27 . The methyl group can be removed subsequently by S N 2 displacement with the help of chloride anion to form intermediate 28 .…”